Skip to main content
SpringerLink
Log in

2,6-hexadecadiynoic acid and 2,6-nonadecadiynoic acid: Novel synthesized acetylenic fatty acids as potent antifungal agents

  • Communications
  • Published:
Lipids

Abstract

The hitherto unknown 2,6-hexadecadiynoic acid, 2,6-nonadecadiynoic acid, and 2,9-hexadecadiynoic acid were synthesized in two steps and in 11–18% overall yields starting from either 1,5-hexadiyne or 1,8-nonadiyne. Among all the compounds 2,6-hexadecadiynoic acid displayed the best overall antifungal activity against both the fluconazole-resistant Candida albicans strains ATCC 14053 and ATCC 60193, with a minimum inhibitory concentration (MIC of 11 μM), and against Cryptococcus neoformans ATCC 66031 (MIC<5.7 μM). 2,9-Hexadecadiynoic acid did not display any significant cytotoxicity against the fluconazole-resistant C. albicans strains, but it showed fungitoxicity against C. neoformans ATCC 66031 with a MIC value of <5.8 μM. Other FA, such as 2-hexadecynoic acid, 5-hexadecynoic acid, 9-hexadecynoic acid, and 6-nonadecynoic acid were also synthesized and their antifungal activities compared with those of the novel acetylenic FA, 2-Hexadecynoic acid, a known antifungal FA, exhibited the best antifungal activity (MIC=9.4 μM) against the fluconazole-resistant C, albicans ATCC 14053 strain, but it showed a MIC value of only 100 μM against C. albicans ATCC 60193. 2,6-Hexadecadiynoic acid and 2-hexadecynoic acid also displayed a MIC of 140–145 μM toward Mycobacterium tuberculosis H37Rv in Middlebrook 7H12 medium. In conclusion, 2,6-hexadecadiynoic acid exhibited the best fungitoxicity profile compared with other analogues. This diynoic FA has the potential to be further evaluated for use in topical antifungal formulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AMB:

amphotericin B

FLC:

fluconazole

LORA:

low oxygen recovery assay

MABA:

microplate alamar blue assay

MIC:

minimum inhibitory concentration

NCCLS:

National Committee for Clinical Laboratory Standards

SDA:

Sabouraud dextrose agar

SDB:

Sabourand dextrose broth

References

  1. Gershon, H., and Shanks, L. (1978) Antifungal Properties of 2-Alkynoic Acids and Their Methyl Esters, Can. J. Microbiol. 24, 593–597.

    Article  PubMed  CAS  Google Scholar 

  2. Gershon, H., and Shanks, L. (1978) Antifungal Activity of Fatty Acids and Derivatives: Structure Activity Relationships, in The Pharmacological Effect of Lipids (J. J. Kabara, ed.), pp. 51–62. American Oil Chemists' Society, Champaign, Illinois.

    Google Scholar 

  3. Konthikamee, W., Gilbertson, J. R., Langkamp, H., and Gershon, H. (1982) Effect of 2-Alkynoic Acids on in vitro Growth of Bacterial and Mammalian Cells, Antimicrob. Agents Chemother. 22, 805–809.

    PubMed  CAS  Google Scholar 

  4. Wood, R., and Lee, T. (1981) Metabolism of 2-Hexadecynoate and Inhibition of Fatty Acid Elongation, J. Biol. Chem. 256, 12379–12386.

    PubMed  CAS  Google Scholar 

  5. Upreti, G. C., Matocha, M., and Wood, R. (1981) Effect 2-Hexadecynoic Acid on Cultured 7288C Hepatoma Cells, Lipids 16, 315–322.

    Article  PubMed  CAS  Google Scholar 

  6. Rudnik, D. A., Lu, T., Jackson-Machelski, E., Hernandez, J. C., Li, Q., Gokel, G. W., and Gordon, J. I. (1992) Analogs of Palmitoyl-CoA That Are Substrates for Myristoyl-CoA: Protein N-Myristoyltransferase. Proc. Natl. Acad. Sci. USA 89, 10507–10511.

    Article  Google Scholar 

  7. Li, X.-C., Jacob, M. R., ElSohly, H. N., Nagle, D. G., Smillie, T. J., Walker, L. A., and Clark, A. M. (2003) Acetylenic Acids Inhibiting Azole-Resistant Candida albicans from Pentagonia gigantifolia. J. Nat. Prod. 66, 1132–1135.

    Article  PubMed  CAS  Google Scholar 

  8. Carballeira, N. M., Sanabria, D., and Parang, K. (2005) Total Synthesis and Further Scrutiny of the in vitro Antifungal Activity of 6-Nonadecynoic Acid. Arch. Pharm. 338, 441–443.

    Article  CAS  Google Scholar 

  9. Wille, J. J., and Kydonieus, A (2003) Palmitoleic Acid Isomer (C16:1 delta6) in Human Skin Sebum Is Effective Against Gram-Positive Bacteria. Skin Pharmacol. Appl. Skin Physiol. 16, 176–187.

    Article  PubMed  CAS  Google Scholar 

  10. Lie Ken Jie, M. S. F., and Lam, C. H. (1978) Fatty Acids. Part XVI. The Synthesis of All Isomeric C18 Furan-Containing Fatty Acids. Chem. Phys. Lipids 21, 275–287.

    Article  CAS  Google Scholar 

  11. Lam, C. H., and Lie Ken Jie, M. S. F. (1975) Fatty Acids. IV. Synthesis of All the Dimethylene-Interrupted Methyl Octadecadiynoates and a Study of Their Gas-Liquid Chromatographic Properties, J. Chromatogr. 115, 559–570.

    Article  PubMed  CAS  Google Scholar 

  12. Galgiani, J. N. (1993) Susceptibility Testing of Fungi: Current Status of the Standardization Process, Antimicrob. Agents Chemother. 37, 2517–2521.

    PubMed  CAS  Google Scholar 

  13. Carballeira, N. M., Ortiz, D., Parang, K., and Sardari, S. (2004) Total Synthesis and in vitro Antifungal Activity of (+/−)-2-Methoxytetradecanoic Acid, Arch. Pharm. (Weinheim) 337, 152–155.

    Article  CAS  Google Scholar 

  14. Nam, N. H., Sardari, S., Selecky, M., and Parang, K. (2004) Carboxylic Acid and Phosphate Ester Derivatives of Fluconazole: Synthesis and Antifungal Activities. Biorg. Med. Chem. 12, 6255–6269.

    Article  CAS  Google Scholar 

  15. Ames, D. E., and Covell, A. N. (1963) Synthesis of Long-Chain Acids. III. Synthesis of Acetylenic Acids, J. Chem. Soc., 775–778

  16. Carballeira, N. M., Cruz, H., Kwong, C. D., Wan, B., and Franzblau, S. (2004) 2-Methoxylated Fatty Acids in Marine Sponges: Defense Mechanism Against Mycobacteria?, Lipids 39, 675–680.

    Article  PubMed  CAS  Google Scholar 

  17. Morbidoni, H. R., Vilcheze, C., Kremer, L., Bittman, R., Sacchettini, J. C., and Jacobs, W. R., Jr (2006) Dual Inhibition of Mycobacterial Fatty Acid Biosynthesis and Degradation by 2-Alkynoic Acids. Chem. Biol. 13, 297–307.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 02881, Kingston, Rhode Island

    Keykavous Parang

  2. Institute for Tuberculosis Research, College of Pharmacy, The University of Illinois at Chicago, 60612-7231, Chicago, Illinois

    Baojie Wan & Scott Franzblau

  3. Department of Chemistry, University of Puerto Rico, PO Box 23346, 00931-3346, San Juan, Puerto Rico

    Néstor M. Carballeira, David Sanabria & Clarisa Cruz

Authors
  1. Néstor M. Carballeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Sanabria
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Clarisa Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keykavous Parang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Baojie Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Scott Franzblau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Néstor M. Carballeira.

About this article

Cite this article

Carballeira, N.M., Sanabria, D., Cruz, C. et al. 2,6-hexadecadiynoic acid and 2,6-nonadecadiynoic acid: Novel synthesized acetylenic fatty acids as potent antifungal agents. Lipids 41, 507–511 (2006). https://doi.org/10.1007/s11745-006-5124-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-006-5124-4

Keywords

Search

Navigation